The nonselective delivery of drugs to both targeted tumor cells and healthy cells is a major shortcoming of current chemotherapies. Enhanced cell targeting during drug delivery could diminish nonspecific toxicities by reducing uptake by healthy cells. Using existing cellular transporters for drug delivery provides opportunities for molecular recognition events to assist in the cell targeting process.
Ever since the published report of the discovery of motuporamines (see 1-3 FIG. 1), naturally occurring anti-cancer agents, found off the coast (Motupore Island) of new Guinea, the molecular structure and their bio-functions have fascinated biochemists (Williams et al., J. Org Chem 1998, 63:4838:4841; Williams et al., J. Org. Chem 2002, 67:245-248; Roskelley et al., Cancer Res. 2001, 61:6788-6794). Indeed, In light of the difficulty and expense of obtaining and purifying natural motuporamines, efforts have been made toward developing analogous compounds having similar or better characteristics that may be synthetically manufactured. Dihydromotuporamine C, (see 4a, FIG. 1) comprises a fifteen-membered ring, which is difficult to synthesize unless one uses expensive metal catalysts like Grubb's catalyst.